Iodine addition products of quinoline carboxylic acids and derivatives thereof



No Drawing.

Patented Get. 20, 1931 JOSEPH EBERT, OF WESTIVEONT, NEW J ERSEY, ASSIGNOR oFFicE TO THE FABASTAN COMPANY,

OFF PHILADELPHIA, PENNSYLVANIA, A COEP GEATION OF PENNSYLVANIA IODINE ADDITION" rnonuc rs or euruoninn cAiaBoxYnro Acins AND DERIVATIVES, THEREOF Y r This invention relates to iodine addition productsof quinoline carboxylic acids and their derivatives, such as the mono-iodo compounds and the di-iodo compounds in which the iodine is loos'elycoupled with the nitrogen of the pyridine nucleus.

I have found that iodine" can be loosely coupled with the nitrogen in the pyridine nucleus of quinoline carboxylic acids and esters of these acids and that the compounds thus formed have valuable medicinal properties, more particularly for the treatment of gout, rheumatism, colds and related ailments. When taken internally these compounds splitoif free iodine instead of liberating hydriodic acidas is the case with inorganic and organic iodides now used. These new compounds have a high eiiectivness'and their use does not involve undesirable secondary actions such as depression of the heart or digestive disorders, Instead, these new compounds have a generaltonic effect onthe system.

More particularly, my invention relates both to iodine addition products of those quinoline carboxylic acids which can be prepared from pyruvic acid, an aryl aldehyde and an organic amine such as aniline. or by the reaction of a ketone such as acetophenone and isatin and to the iodine additionproducts of esters of these quinoline carboxylic acids. The preparation of quinoline carboXylic acids by these methods is well known in the art as evidenced by the references in Beilstein, 3rd edition, vol. 4, page4i5. Tn quinolinecarboxylic acids prepared by either of these methods, the carboxylic acid group is in the 4: position and the hydrogen of the 2 position is substituted by an aryl group. By varying the starting materials, various aryl groups may be substituted in'the 2 posi-v tion and alkyl groups maybe introduced into the 6 position. The iodine additionproducts of these compounds may be represented by the general formula 000R R1 Application filed Deceinber 30, 1929. serial No. 417,694.

in which B may be hydrogenior an alltyl group, R may be hydrogen or an alkyl group, R is an aryl group and X may be one or. two. The reaction with iodine may be so carried out that a mixture of the monoiodo and di-iodo compounds is obtained.

The iodine addition-products may be prepared by suspending the acid or ester in an alcoholic or aqueous solution containing a suitable amount of iodine at a, temperature preferably betweenlabout l5 and (l, for about 12 to2 l hours or until the desired amountof iodiiielias become coupled with the nitrogen ofthe pyridine nucleus. The mixture may thenbe diluted with water and acidified to separate the new"cempou1id .-"The compound is then filteredoff and washed with cold water and subsequently dried at a low temperature. In place of employing iodine, iodine-furnishingmaterials may be used; The reaction products are in general of a reddish brown, darkbrown or greenish brown color. They are generallysubstantially insoluble-in water but soluble in certain 0rgan'icsolvents such as alcohol and acetone. The iodine isloosely'cou'pled with the quinoline carboxylic acids and esters and when the iodine addition products are mildly heated they gradually liberate iodine. At high temperatures they decompose with formation of complex iodine and /oxidation products. The invention will be further illustrated by the following examplesi I. 2-phenyl-mono-iodo-quinoline-L-carboxylic acid coon 2.5 parts by weight of 2-phenyLquinOline-4- carboxylic acid (cinchophen, which may be made from aniline, benzaldehyde and vy- (depending on the rate of heating) decomposition takes place with formation of complex iodine and oxidation products.

IL 2-phenyl-di-iodo quinoline 4 canboxylicacid 2.5.iparts by weight of 2r-phenyl-quinoline4- carboxylicacid zcinchophen) are suspended int-a solution of 2.54 parts by 'weight of iodine inzethyl. alcohol. and, agitated-1 at a temperatureof fromv1 5 to 50 C..fr about 24 to 50 hours,. or until the supernatant solution 'is slightlyyellow'. The reaction'mass is worked up in: the same manner as in: Example. I.

The new compound is of; aadark brown color, 7 contains about 50% of.1odme,.and1s soluble in the same solvents as A coinpoun'dzNo. I. On heating, the compoundthe same behavior as-the mono-compound;

In a similar" manner the mono-iodo and.

di-iodo-addition.products of both the methyl and ethyl esters of.QTphenyl quinolineAreal- 'boxylic acid can be preparedthus:

shows substantially (which may be made by esterifying the acid obtained from paratoluidine, benzaldehyde and pyruvic acid) are suspended in a solution of 1.27 parts by weight of iodine in ethyl. alcohol and. agitated. at a temperature offroml to 50 C. fonaboutamvto Qihours, or until the color of the supernatant solution has become yellow. The mixture is diluted with. water: and acidifiedx. with. 4.. parts by Weight of a. HCL; The precipitate is collected on a filter, washed with cold water and dried at a low'temperature." The new compound is of dark brown or greenishbrown color,.contains about iodine, is substantially insoluble in Water, soluble in alcohols and'ac'etone. ()n heatingit starts tomelt atabout (1, about 1 this temperature dBCOlllPOSltlOIl takes place.

The 6 methyl12=phenyl-di iodo quinoIinehcarboxylici acid ethyl ester hasbeen prepared in an analogousmanner. It contains about146.6% iodine:

G O O H 1 CH O h from fi-methoxy 2-phenylquino- 3 line l-carboxylic acid (p-enisidine, benzaldehyde and pyruvic C 0115 aci (l) ftom=methyl ester 0! the same.

fromethyl ester of the same.

from G-ethoxy-Z-phenylquinoline- 4fcarboxylic= acid (ppheuetiding,- 'bQlllflldQhYdB and pyruvic aci from methyl ester of the same.

IHaO 7 from ethyl ester of the same. CuHu III v Ix I from 2-oxypheny1quinoliue-4-cargoixlylcacgi (aniline, s gglcylale y e an pyruvic acl N CsH4.OH V

0 O OH from 2-toluylquinoline-4-carboxylic acid (aniline, a-toluyla'; OHLCHB dehyde and pyruvic acid).

N I X 0 O OH from 2-cinnamylquino1ine- Q-carboxylic acid (aniline, cinnamicaldehyde and CH.CH.O1H| pyruvic acid).

N I x O O OH CH? from 6-methyl-2-oxyphenylquinoline-4-carboxylic acid O0H40H Vic acid).

carboxylic acids and esters in which the iodine is loosely coupled with the nitrogen of the pyridine nucleus.

2. Iodine addition products with the general formula in which R is hydrogen or an alkyl group, R is an alkyl group and R is hydrogen, aryl or an aralkyl group and X is 1 to 2. 3. Iodine addition products with the general formula V B: N V

in which R is hydrogen or an akyl group, R

is an aryl group, and X is 1 0r (p-tolui- V dme, s alicylaldehyde and pyru-' 4. Iodine addition products with the general formula OOOH ON 00H! i In witness whereof, I have subscribed my name.

JOSEPH EBERT. 

